A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease

Background Platelet inhibition is important for patients with coronary artery disease. When dual antiplatelet therapy (DAPT) is required, a P2Y.sub.12-antagonist is usually recommended in addition to standard aspirin therapy. The most used P2Y.sub.12-antagonists are clopidogrel, prasugrel and ticagr...

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Bibliographic Details
Published in:Thrombosis journal 2019-05, Vol.17 (1), p.1-9, Article 11
Main Authors: Warlo, Ellen M. K, Arnesen, Harald, Seljeflot, Ingebjarg
Format: Article
Language:English
Subjects:
Acute coronary syndromes
Aspirin
Binding sites
Blood platelets
Cardiac patients
Cardiovascular disease
Care and treatment
Clinical medicine
Clopidogrel
Coronary heart disease
Coronary vessels
Cytochrome
Drug dosages
Drug interactions
Drug resistance
Genetic polymorphisms
Heart attacks
Intervention
Laboratories
Metabolism
Metabolites
P2Y12 receptor antagonists
Platelet aggregation inhibitors
Prasugrel
Residual platelet reactivity
Review
Ticagrelor
Vasodilator agents
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Summary:Background Platelet inhibition is important for patients with coronary artery disease. When dual antiplatelet therapy (DAPT) is required, a P2Y.sub.12-antagonist is usually recommended in addition to standard aspirin therapy. The most used P2Y.sub.12-antagonists are clopidogrel, prasugrel and ticagrelor. Despite DAPT, some patients experience adverse cardiovascular events, and insufficient platelet inhibition has been suggested as a possible cause. In the present review we have performed a literature search on prevalence, mechanisms and clinical implications of resistance to P2Y.sub.12 inhibitors. Methods The PubMed database was searched for relevant papers and 11 meta-analyses were included. P2Y.sub.12 resistance is measured by stimulating platelets with ADP ex vivo and the most used assays are vasodilator stimulated phosphoprotein (VASP), Multiplate, VerifyNow (VN) and light transmission aggregometry (LTA). Discussion/conclusion The frequency of high platelet reactivity (HPR) during clopidogrel therapy is predicted to be 30%. Genetic polymorphisms and drug-drug interactions are discussed to explain a significant part of this inter-individual variation. HPR during prasugrel and ticagrelor treatment is estimated to be 3-15% and 0-3%, respectively. This lower frequency is explained by less complicated and more efficient generation of the active metabolite compared to clopidogrel. Meta-analyses do show a positive effect of adjusting standard clopidogrel treatment based on platelet function testing. Despite this, personalized therapy is not recommended because no large-scale RCT have shown any clinical benefit. For patients on prasugrel and ticagrelor, platelet function testing is not recommended due to low occurrence of HPR. Keywords: P2Y12 receptor antagonists, Residual platelet reactivity, Clopidogrel, Prasugrel, Ticagrelor
ISSN:1477-9560
1477-9560
DOI:10.1186/s12959-019-0197-5